Approximately 1,000,000 aortocoronary and peripheral vascular revascularizations are performed each year using human saphenous vein (HSV). The leading cause of graft failure is the subsequent development of intimal hyperplasia. Surgical techniques typically employed for HSV harvest cause injury. These injurious techniques include stretching the vein (longitudinally during harvest and by manual high-pressure intraluminal distension), placing the vein heparinized saline (pH 6.2) after harvest and the use of surgical skin markers applied to the vein (which contain isopropyl alcohol) to properly orient the vein graft. Preliminary data has shown that 40% of HSV harvested for coronary artery bypass procedures have no functional viability. The hypothesis of this proposal is that preventing injury to the vein during harvest will decrease the subsequent development of intimal hyperplasia. This proposal will 1) determine the mechanisms underlying the loss of functional viability of vein grafts;2) determine if injury to the vein graft leads to the development of intimal hyperplasia in a rabbit carotid interposition vein graft model. While many investigators have suggested that injury is deleterious to the conduit, this notion has not been proven in vivo. Accomplishment of these goals would provide a platform for future clinical trials with simple straightforward interventions that would improve graft patency. This would have a significant impact on the morbidity, mortality, and costs associated with vein graft failure. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is one of the leading causes of death and disability in the United States. Our research could potentially increase the time a bypass graft stays open, and lessen the morbidity and mortality of vein graft failure.